ADAMTS -1 and -4 are up-regulated following transient middle cerebral artery occlusion in the rat and their expression is modulated by TNF in cultured astrocytes

CROSS, A. K., HADDOCK, G., STOCK, C. J., ALLAN, S., SURR, J., BUNNING, R. A., BUTTLE, D. J. and WOODROOFE, N. (2006). ADAMTS -1 and -4 are up-regulated following transient middle cerebral artery occlusion in the rat and their expression is modulated by TNF in cultured astrocytes. Brain research, 1088 (1), 19-30.

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        Link to published version:: 10.1016/j.brainres.2006.02.136

        Abstract

        ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) enzymes are a recently described group of metalloproteinases. The substrates degraded by ADAMTS-1, -4 and -5 suggests that they play a role in turnover of extracellular matrix in the central nervous system (CNS). ADAMTS-1 is also known to exhibit anti-angiogenic activity. Their main endogenous inhibitor is tissue inhibitor of metalloproteinases (TIMP)-3. The present study was designed to investigate ADAMTS-1, -4 and -5 and TIMP-3 expression after experimental cerebral ischaemia and to examine whether cytokines known to be up-regulated in stroke could alter their expression by astrocytes in vitro. Focal cerebral ischaemia was induced by transient middle cerebral artery occlusion in the rat using the filament method. Our results demonstrate a significant increase in expression of ADAMTS-1 and -4 in the occluded hemisphere but no significant change in TIMP-3. This was accompanied by an increase in mRNA levels for interleukin (IL)-1, IL-1 receptor antagonist (IL-1ra) and tumour necrosis factor (TNF). ADAMTS-4 mRNA and protein was up-regulated by TNF in primary human astrocyte cultures. The increased ADAMTS-1 and -4 in experimental stroke, together with no change in TIMP-3, may promote ECM breakdown after stroke, enabling infiltration of inflammatory cells and contribute to brain injury. In vitro studies suggest that the in vivo modulation of ADAMTS-1 and -4 may be controlled in part by TNF.

        Item Type: Article
        Additional Information: Published version available at: http://www.sciencedirect.com/science/journal/00068993
        Uncontrolled Keywords: cytokine
        Research Institute, Centre or Group: Biomedical Research Centre
        Identification Number: 10.1016/j.brainres.2006.02.136
        Depositing User: Ann Betterton
        Date Deposited: 02 Oct 2007
        Last Modified: 21 Dec 2010 11:30
        URI: http://shura.shu.ac.uk/id/eprint/403

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